Regarding the treatment of cancers, in addition to the common therapeutic methods such as surgery, chemotherapy, radiation therapy and target gene therapy, immunotherapy has been considered as the most breakthrough anti-cancer strategy in recent years. Immunotherapy refers to that the autoimmune system is activated by an artificial manner, to recognize and attack cancer cells, so as to subject tumors to shrink or disappear and prolong patient's life span.
Clinical researches have shown that although immunotherapy shows quite good efficiency, some patients are insensitive to immunotherapy. For example, it was found in melanoma clinical researches that immune cells cluster around the tumor but cannot get into the tumor. In this respect, Dr. Tasuku Honjo and Dr. James P. Allison discovered that some cancer cells can induce immune cells to initiate a suppression of immune response through the surface antigen of cancer cells (e.g. PDL-1, CTLA-4), and thus both the autologous and exogenous immune cells cannot be activated. The surface antigen of cancer cells, such as programmed death-ligand 1 (PDL-1) and cytotoxic T lymphocyte associated protein 4 (CTLA-4), are also called immune checkpoint antigens.
To solve the above problems, Dr. Tasuku Honjo and Dr. James P. Allison collaboratively developed an antibody which is capable of neutralizing programmed death 1 (PD-1) on the surface of T cells, so as to disable the PDL-1 on the surface of cancer cells from binding to immune cells or further subjecting immune cells to die, and thus, can be used in therapy. However, it was found in a test that the block of PD-1 expression of T cells may easily result in an imbalance of immune cell regulatory mechanism in patients, and thus, result in patient's death. Therefore, some researchers think reversely to develop antibodies which can inhibit the expressions of immune checkpoint antigens on the surface of cancer cells for use in therapy.
For example, Ipilimumab is an immune checkpoint inhibitor. Results of the phase ill clinical trial showed that, with the administration of Ipilimumab alone, the overall survival rate of patients with stage three or four melanoma increased by 10.1 months, and that also proved the importance of immune checkpoints for cancer immunotherapy. However, the disadvantage in developing antibodies which can inhibit the expressions of immune checkpoint antigens is that the cost is quite high and the steps are complex. Therefore, there is a necessity and urgency for continuously developing a drug or method for inhibiting immune checkpoint antigens effectively.
Inventors of the present invention found that Z-BP is effective in inhibiting the expressions of immune checkpoint antigens of cancer cells, promoting cancer cells to secret chemokines capable of activating the immune system, increasing the amount of immune cells, and promoting the entry of immune cells into the tumor site, and thus, can be used for activating autoimmune system. Furthermore, inventors unexpectedly found that, the therapeutic efficacy of administering to a cancer subject Z-BP and mononuclear cells is much better than administering mononuclear cells alone.